Methylene blue (ProvayBlue) is a thiazine dye that's FDA approved to treat methemoglobinemia, a serious condition where red blood cells can’t deliver oxygen properly to the body. It's also used off-label for conditions like malaria, shock, and as a diagnostic aid for imaging. The medication is typically given intravenously (IV) by a healthcare professional to adults and children who are in the hospital. The dosage is based on body weight. Side effects include headache, diarrhea, and low potassium or magnesium levels in the blood.
High methemoglobin levels (methemoglobinemia) in adults and children
Hemoglobin is a protein that carries oxygen throughout the body. Sometimes, when the body is exposed to certain medications or chemicals, it can create a different form called methemoglobin. Methemoglobin can’t carry oxygen, and too much of it leads to a serious condition called methemoglobinemia.
Methylene blue (ProvayBlue) is a thiazine dye. It works to treat methemoglobinemia by changing methemoglobin back to hemoglobin, so it can carry oxygen to the body.
Source: DailyMed
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor or nurse immediately if any of the following side effects occur:
Incidence not known
Agitation
bluish-colored lips, fingernails, or palms
confusion
dark urine
difficulty breathing
difficulty swallowing
dizziness or lightheadedness
fast heartbeat
headache
hives or welts, itching, or skin rash
large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
overactive reflexes
pale skin
poor coordination
rapid heart rate
redness of the skin
restlessness
shivering
sweating
talking or acting with excitement you cannot control
tightness in the chest
trembling or shaking
twitching
unusual bleeding or bruising
unusual tiredness or weakness
Get emergency help immediately if any of the following symptoms of overdose occur:
Symptoms of overdose
Abdominal or stomach pain
bigger, dilated, or enlarged pupils (black part of the eye)
blue staining of the urine, skin, and mucous membranes
bluish-colored lips, fingernails, or palms
blurred vision
burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
confusion
dark urine
difficulty breathing
dizziness or lightheadedness
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
fear
headache
increased sensitivity of the eyes to light
pale skin
rapid heart rate
rapid shallow breathing
shakiness in the legs, arms, hands, or feet
tightness in the chest
unusual bleeding or bruising
unusual tiredness or weakness
vomiting
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Change in taste
changes in skin color
feeling hot or cold
increased sweating
loss of taste
muscle or joint pain
pain at the infusion site
pain in the arms or legs
Less common
Back pain
bruising
chills
general feeling of discomfort or illness
large, flat, blue or purplish patches in the skin
loss of appetite
muscle aches and pains
trouble sleeping
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Typically only given for 1 or 2 doses
Works quickly to relieve symptoms
Can be used in children and adults
Needs to be given as an infusion by a healthcare professional
Not safe during pregnancy or breastfeeding
Can turn your skin and body fluids blue
Your healthcare professional will give you methylene blue (ProvayBlue) as an IV injection over 5 to 30 minutes. Afterward, they’ll check your methemoglobin levels and look for symptoms of methemoglobinemia to decide if you need another dose.
People with G6PD deficiency are more likely to develop low red blood cell counts (hemolytic anemia) while taking methylene blue (ProvayBlue). They also might not respond well to the medication. Let your care team know if you have G6PD deficiency.
Methylene blue (ProvayBlue) can cause dizziness, confusion, and changes in vision. Avoid driving or doing tasks that require concentration until these side effects go away.
Methylene blue (ProvayBlue) has a dark blue color, which can turn your skin or body fluids blue. This discoloration can last for an unknown period, with some cases lasting over 3 years.
Methylene blue (ProvayBlue) can make your skin more sensitive to sunlight. Use sunscreen and wear long-sleeve clothing for a few days after treatment to protect your skin from sunburns.
Methylene blue (ProvayBlue) interacts with many medications, especially medications that raise serotonin and dapsone. Tell your care team about everything you’re taking, including prescription and over-the-counter medications.
Let your care team know if you're pregnant. Methylene blue (ProvayBlue) isn't recommended during pregnancy because there's a potential risk it can harm the unborn baby. Your care team will likely consider other treatment options.
There's not much information about the safety of methylene blue (ProvayBlue) during breastfeeding. But to avoid potential harm, don’t breastfeed for at least 8 days after your last dose.
Methylene blue (ProvayBlue) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Risk factors: Taking other medications that raise serotonin levels in your brain
Some people who received methylene blue (ProvayBlue) developed a rare but serious condition called serotonin syndrome. This condition happens where there's too much serotonin in the brain. Your risk is higher if you take methylene blue (ProvayBlue) with other medications that can raise your serotonin levels, such as certain antidepressants, mental health medications, pain medications, and migraine medications. Tell your care team about all the medications you take before starting methylene blue (ProvayBlue). Symptoms of serotonin syndrome include fast heart rate, sweating, muscle stiffness or spasms, fever, and confusion. Let your care know right away if you have any of these symptoms.
Severe allergic reactions to methylene blue (ProvayBlue) are possible, including life-threatening reactions like facial swelling, shock, and anaphylaxis. Let your care team know right away if you notice hives, swelling of the lips or tongue, or difficulty breathing after receiving this medication.
Methylene blue (ProvayBlue) can cause hemolytic anemia, which is when your red blood cells are broken down. This can happen 1 or more days after receiving the injection, and some people have had to get red blood cell transfusions to treat it. Your healthcare team will monitor your blood cell counts before and during treatment. Let them know if you have symptoms such as tiredness, dizziness, and weakness.
Methylene blue (ProvayBlue) can cause confusion, dizziness, and vision problems. Avoid driving or doing anything dangerous until these side effects go away. Talk to your prescriber if you have concerns.
The typical dose is 1 mg/kg of body weight injected through the veins (IV) over 5 to 30 minutes.
If your methemoglobin level stays above 30%, or you still have methemoglobinemia symptoms (e.g., shortness of breath, fast heart rate, weakness), your care team will consider repeating the dose after an hour, as long as you don't have kidney problems.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
People with G6PD deficiency
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American Regent, Inc. (2024). ProvayBlue- methylene blue injection [package insert]. DailyMed.
Gumus, M., et al. (2013). How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye. Breast Care.
MedlinePlus. (2023). Glucose-6-phosphate dehydrogenase deficiency.
MedlinePlus. (2023). Shock.
MedlinePlus. (2024). Methemoglobinemia.
MedlinePlus. (2024). Serotonin syndrome.
National Cancer Institute. (n.d.). Hemoglobin.
National Heart, Lung, and Blood Institute. (2022). Hemolytic anemia.
Rehman, H. U. (2001). Methemoglobinemia. The Western Journal of Medicine.
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